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Medicine & Science in Sports & Exercise:
doi: 10.1249/MSS.0000000000000405
Original Investigation: PDF Only

Mesenchymal Stem Cells Augment the Adaptive Response to Eccentric Exercise.

Zou, Kai; Huntsman, Heather D.; Valero, M. Carmen; Adams, Joseph; Skelton, Jack; De Lisio, Michael; Jensen, Tor; Boppart, Marni D.

Published Ahead-of-Print
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Abstract

Purpose: The [alpha]7[beta]1 integrin is a transmembrane protein expressed in skeletal muscle that can link the actin cytoskeleton to the surrounding basal lamina. We have previously demonstrated that transgenic mice overexpressing the [alpha]7B integrin in skeletal muscle (MCK:[alpha]7B; [alpha]7Tg) mount an enhanced satellite cell and growth response to single or multiple bouts of eccentric exercise. Additionally, interstitial stem cells characterized as mesenchymal stem cells (MSCs) accumulate in [alpha]7Tg muscle (mMSCs) in the sedentary state and post-exercise. The results from these studies prompted us to determine the extent to which mMSCs underlie the beneficial adaptive responses observed in [alpha]7Tg skeletal muscle post-exercise.

Methods: mMSCs (Sca-1+CD45-) were isolated from [alpha]7Tg mice, dye-labeled, and intramuscularly injected into adult wild type recipient mice. Following injection of mMSCs or saline, mice remained sedentary (SED) or were subjected to eccentric exercise training (TR) (downhill running) on a treadmill (3X/week) for two or four weeks. Gastrocnemius-soleus complexes were collected 24 hours after the last bout of exercise.

Results: mMSCs did not directly fuse with existing fibers, however, mMSC injection enhanced Pax7+ satellite cell number and myonuclear content compared to all other groups at two weeks post-exercise. Mean CSA, percentage of larger caliber fibers (>3000 [mu]m2) and grip strength were increased in mMSC/TR compared to Saline/SED and mMSC/SED at four weeks. mMSC transplantation did not enhance repair or growth in the absence of exercise.

Conclusion: The results from this study demonstrate that mMSCs contribute to beneficial changes in satellite cell expansion and growth in [alpha]7Tg muscle following eccentric exercise. Thus, MSCs that naturally accumulate in muscle following eccentric contractions may enhance the adaptive response to exercise.

(C) 2014 American College of Sports Medicine

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